Refractive surgery refers to a set of surgical procedures that change the native optical or focusing power of the eye. These changes alleviate the need for glasses or contact lenses that an individual might otherwise be dependent on for clear sight. The majority of the focusing power in the human eye is dictated by the curvature of the air-liquid interface, where there is the greatest change in the index of refraction. This curved interface is the outer surface of the cornea. The refractive power of this interface accounts for approximately 70% of the total magnification of the eye. Light rays that make up the images we see pass through the cornea, the anterior chamber, the crystalline lens, and the vitreous humor before they are focused on the retina to form an image. It is the magnifying power of this curved, air-corneal interface that provided the field of refractive surgery with the opportunity to surgically correct visual deficiencies.
Initial refractive surgical procedures corrected nearsightedness by flattening of the curvature of the cornea. The first largely successful procedure was called radial keratotomy (RK). RK was widely used during the 1970's and early 1980's where radially oriented incisions were made in the periphery of the cornea. These incisions allowed the peripheral cornea to bow outwards, consequently flattening the central optical zone of the cornea. This was fairly easy and thus, popular, but it rarely did more than lessen one's dependency on glasses or contract lenses.
A largely flawed and failed procedure called epikeratophakia was developed in the era of RK. It is now essentially an academic anomaly. Epikeratophakia provided a new curvature to the outer curvature of the cornea by grafting onto the cornea a thin layer of preserved corneal tissue. Lyophilization is the preservation method used in epikeratophakia where the cornea is freeze-dried. The tissue is not acellularized but is rendered non-living. During the process of freeze drying, the cornea is also ground to a specific curvature.
The epikeratophakia lens was placed into the eye surgically. An annular 360° incision was placed into the cornea after completely removing the epithelium from where the epikeratophakic lens would sit. The perimeter of this lens would be inserted into the annular incision and held in place by a running suture. There were several problems with epikeratophakia: 1) the lenses remained cloudy until host stromal fibroblasts colonized the lens, which colonization possibly could take several months; 2) until migrating epithelium could grow over the incision site onto the surface of the lens, the interrupted epithelium was a nidus for infection; and 3) epithelium healing onto the surgical site sometimes moved into the space between the lens and the host cornea. Currently, epikeratophakia is limited in its use. It is now used in pediatric aphakic patients who are unable to tolerate very steep contact lenses.
Major industrial research efforts tried to produce a synthetic version of the epikeratophakic graft called the synthetic onlay in a synthetic epilens. Development of synthetic epikeratophakia was undertaken in order to make a viable refractive product (i.e. adequate raw materials for mass production and quality control for operations). Different synthetic polymers were used (hydroxyethylmethacrylate, polyethylene oxide, lidofilcon, polyvinyl alcohol). Hydrogels of these materials normally did not have a surface that was readily conducive to epithelial cells growing and adhering onto these synthetic surfaces. This was one of the major setbacks of synthetic onlays. Epithelial cells could not adequately heal onto these lenses. The success of any epikeratophakia procedure is dependent on epithelial wound healing and epithelial coverage over the surface not covered by the epithelium, typically at least the implant surface.
Another problem with those previous synthetic lenses is that they did not adhere well to the surface of the eye. Conventional suturing was difficult and the use of biological glues was also flawed. Glues were not ideally biocompatible in the cornea.
Lastly, the permeability of these hydrogels was significantly limiting. Living epithelial cells on the surface had difficulty achieving adequate nutrition. Corneal epithelial nutritional flow is from the aqueous humor through the cornea out to the epithelial cells. In the end, industrial efforts failed to develop an adequate synthetic epikeratophakic lens.
Around the mid-1990's, procedures that sculpt the cornea with lasers were sufficiently successful that they began to replace radial keratotomy. The first generation of laser ablation of the cornea was called photorefractive keratectomy (PRK). In PRK, an ablative laser (e.g., an excimer laser) is focused on the cornea to sculpt a new curvature into the surface. In PRK, the epithelium is destroyed when achieving a new outer surface curve. Over the ensuing post-operative days, the epithelium has to grow or heal back into place. This epithelial healing phase was problematic for most patients since the epithelially denuded and ablated cornea was painful. It is also initially difficult to see, and this “recuperative time” can last from days to a week or more.
A subsequent variation of PRK corneal laser ablation, LASIK, has become very popular. The LASIK procedure, also known as LASer In situ Keratomileusis (LASEK), is synonymous in the public mind with laser vision correction. In LASIK, an outer portion (or chord-like lens-shaped portion) of the cornea (80 to 150 microns thick) is surgically cut from the corneal surface. This is performed by a device called a microkeratome. The microkeratome is a device which cuts a circular flap from the surface of the cornea that remains hinged at one edge. This flap is reflected back and an ablative (excimer) laser is used to remove or to reform a portion of the exposed surgical bed. The flap is laid back into place. When this flap is laid back into place, the cornea achieves a new curvature because the flap conforms to the laser-modified surface. In this procedure, epithelial cells are not removed or harmed. The epithelial cells have simply been incised at the edge of this flap. When the flap is placed back onto the corneal bed, the epithelium heals back at the incision site. There is essentially no recuperative time and the results are almost immediate. Because there is very little surgical time (15 minutes for each eye) and because there are lasting and very accurate results, LASIK is currently considered the premier manner of performing refractive surgery.
The newest technique being evaluated in high volume refractive surgical practices and in some academic centers is a procedure called Laser Assisted Subepithelial Keratomileusis (LASEK). In LASEK, a “flap” is made of only epithelium. This layer of epithelium is lifted off the cornea in a manner similar to LASIK. The ablative laser is focused just on the surface of the denuded cornea (in the same manner as was done with PRK). However, this epithelial flap is left intact, i.e., epithelium is not destroyed. It is simply rolled back into place after formation of the re-curved anterior portion of the cornea, resulting in much less recuperative time than with PRK. Current methods of LASEK are not as good as LASIK but the results are better than with PRK.
The corneal epithelium is a multilayered epithelial structure typically about 50 μm in thickness. It is non-cornified. The outer cells are living, although they are squamous in nature. The basal epithelial cells are cuboidal and sit on the stromal surface on a structure known as Bowman's membrane. The basal cell layers is typically about 1 mil thick (0.001″). The basal cells produce the same keratins that are produced in the integument, i.e., skin. The basal epithelial cells express keratins 5 and 14 and have the potential to differentiate into the squamous epithelial cells of the corneal epithelium that produce keratins 6 and 9. The corneal epithelium has a number of important properties: 1) it is clear; 2) it is impermeable; 3) it is a barrier to external agents; and 4) it is a highly innervated organ. Nerves from the cornea directly feed into the epithelium, and thus, defects of this organ produce pain.
Epithelial cells are attached side-to-side by transmembrane molecules called desmosomes. Another transmembrane protein, the hemidesmosome, connects to collagen type 7 and is present on the basolateral surface of basal epithelial cells. Hemidesmosomes anchor epithelium to the underlying collagenous portion of the stroma. The junction between the epithelium and corneal stroma is referred to as basement membrane zone (BMZ).
When LASEK is performed, a physical well is placed or formed on the epithelium and filled with a selection of 20 percent ethanol and balanced salt solution. Contact with the solution causes the epithelial cells to lose their adherence at the BMZ, most likely by destroying a portion of that cell population. The epithelium is then raised by pushing the epithelium, e.g., with a Weck sponge, in a manner similar to striping a wall of paint. The exposed collagenous portion of the corneal stroma is then ablated to reshape its surface. A weakened epithelium is then rolled back into place to serve as a bandage. However, this “bandage” fails to restore the epithelium to its original state, i.e., it does not preserve the integrity of the epithelium, thereby reducing its clarity, impermeability to water, and barrier function. Furthermore, the ability of the epithelium to adhere to the corneal stromal surface is impaired.
U.S. Pat. Nos. 6,099,541 and 6,030,398 to Klopotek describe an microkeratome apparatus and method for cutting a layer of corneal epithelium to prepare the eye for LASIK or other reshaping procedures. The epithelium, if replaced, is attached using surgical techniques.
None of the cited references shows or suggests my invention as described herein.